Nature Research, Nature Genetics, 3(45), p. 295-298, 2013
DOI: 10.1038/ng.2552
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One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1 in six further individuals with spinal meningiomas identified two additional heterozygous loss-of-function mutations. Tumors from individuals with SMARCE1 mutations were of clear-cell histological subtype, and all had loss of SMARCE1 protein, consistent with a tumor suppressor mechanism. Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology. ; Smith, Miriam J O'Sullivan, James Bhaskar, Sanjeev S Hadfield, Kristen D Poke, Gemma Caird, John Sharif, Saba Eccles, Diana Fitzpatrick, David Rawluk, Daniel du Plessis, Daniel Newman, William G Evans, D Gareth HL-102923/HL/NHLBI NIH HHS/United States HL-102924/HL/NHLBI NIH HHS/United States HL-102925/HL/NHLBI NIH HHS/United States HL-102926/HL/NHLBI NIH HHS/United States HL-103010/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Nature genetics Nat Genet. 2013 Mar;45(3):295-8. doi: 10.1038/ng.2552. Epub 2013 Feb 3.